arthrogryposis, renal dysfunction, and cholestasis 2

Arthrogryposis, renal dysfunction, and cholestasis 2 is a multi-system condition that affects the liver, kidneys, and musculoskeletal system. The condition is caused by mutations in the VIPAS39 gene, and it follows an autosomal recessive inheritance pattern. Affected individuals present in infancy with multiple metabolic and organ dysfunctions, and while precise prevalence estimates are not well established, the features are consistently observed in those affected. Overall, the condition is characterized by a distinctive combination of cholestatic liver disease, renal abnormalities, and joint contractures.

Individuals with arthrogryposis, renal dysfunction, and cholestasis 2 typically exhibit a range of clinical features. The condition is marked by metabolic acidosis, cholestatic liver disease, aminoaciduria, hepatomegaly, glycosuria, arthrogryposis multiplex congenita, pruritus, and proteinuria, which are consistently observed. In addition, a subset of patients may develop nephrogenic diabetes insipidus and lissencephaly. Not all individuals experience every feature and severity varies considerably, making clinical management highly individualized.

This condition is caused by pathogenic variants in the VIPAS39 gene. The VIPAS39 gene plays an important role in cellular processes that affect the function of multiple organ systems including the liver, kidneys, and musculoskeletal tissues. It is inherited in an autosomal recessive manner, meaning that an affected individual has received one altered copy of the gene from each parent, and there is a 25% recurrence risk for each pregnancy in families where both parents carry the mutation. Genetic counseling is recommended for families to understand these risks and implications.

Currently, management focuses on supportive care and symptom management. Treatment is tailored to each individual and typically involves a multidisciplinary team to address the various organ systems affected. Regular surveillance is an essential part of long-term care to monitor liver, kidney, and musculoskeletal function, and genetic counseling is advised to assist families with understanding the condition and family planning. Patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate for their specific situation.

The clinical course of arthrogryposis, renal dysfunction, and cholestasis 2 can vary widely between individuals. Some patients may experience complications related to multi-system involvement while others benefit from periods of relative stabilization with supportive care. With current standards of care, many individuals achieve an improved quality of life, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition for ongoing guidance and support.